目的 对青蒿Artemisiae Annuae Herba中酚酸类成分进行系统研究。方法 综合应用各种现代色谱分离技术进行系统的分离纯化，根据化合物的理化性质和核磁共振波谱数据进行结构鉴定，并通过分子对接技术和酶活性检测的方法，对分离得到的咖啡酰奎宁酸类化合物进行了靶向磷酸二酯酶的抑制活性研究。结果 从青蒿水提取物经HP-20大孔吸附树脂50%乙醇洗脱部位中共分离鉴定20个咖啡酰奎宁酸类化合物，分别为4-O-咖啡酰基-5-O-阿魏酰奎宁酸甲酯（1）、3-O-阿魏酰奎宁酸（2）、3-O-阿魏酰奎宁酸甲酯（3）、4-O-阿魏酰奎宁酸甲酯（4）、5-O-阿魏酰奎宁酸甲酯（5）、3,4-O-二咖啡酰奎宁酸（6）、3-O-咖啡酰基-4-O-阿魏酰奎宁酸（7）、3,4-O-二阿魏酰奎宁酸甲酯（8）、3,5-O-二咖啡酰奎宁酸（9）、3-O-阿魏酰基-5-O-咖啡酰奎宁酸甲酯（10）、1-O-咖啡酰基-3-O-阿魏酰奎宁酸（11）、1,3-O-二阿魏酰奎宁酸（12）、1,5-O-二咖啡酰奎宁酸（13）、1-O-咖啡酰基-5-O-阿魏酰奎宁酸（14）、4,5-O-二咖啡酰奎宁酸（15）、4-O-阿魏酰基-5-O-咖啡酰奎宁酸（16）、4-O-咖啡酰基-5-O-阿魏酰奎宁酸（17）、4-O-阿魏酰基-5-O-咖啡酰奎宁酸甲酯（18）、4,5-O-二阿魏酰奎宁酸（19）、3,4,5-O-三咖啡酰取代奎宁酸（20）；分离得到的奎宁酸类化合物对磷酸二酯酶的不同亚型蛋白具有较好的抑制潜力，其中化合物9对磷酸二酯酶PDE4B的抑制活性半数抑制浓度（median inhibition concentration，IC₅₀）值在0.36 μmol/L左右。结论 化合物1为新化合物，命名为青蒿酸A，化合物3～5、8、10～12、14、18为首次从蒿属植物中分离得到，该类化合物具有靶向抑制磷酸二酯酶的作用。

Objective To study the phenolic acids from Qinghao (Artemisiae Annuae Herba). Methods The chemical constituents were isolated by various chromatographic techniques and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literatures. The obtained compounds were further applied in the inhibition activity studies targeted on phosphodiesterase through molecular docking technology and enzyme inhibitory activity assays. Results The water extract of Artemisiae Annuae Herba was subjected to HP-20 macroporous adsorption resin to yied 50% ethanol fraction. Twenty caffeoylquinic acids were obtained and characterized as 4-O-caffeoyl-5-O-feruloylquinic methyl ester (1), 3-O-feruloylquinic acid (2), 3-O-feruloylquinic methyl ester (3), 4-O-feruloylquinic methyl ester (4), 5-O-feruloylquinic methyl ester (5), 3,4-di- O-caffeoylquinic acid (6), 3-O-caffeoyl-4-O-feruloylquinic acid (7), 3,4-di-O-feruloylquinic methyl ester (8), 3,5-di-O-caffeoylquinic acid (9), 3-O-feruloyl-5-O-caffeoylquinic methyl ester (10), 1-O-caffeoyl-3-O-feruloylquinic acid (11), 1,3-di-O-feruloylquinic acid (12), 1,5-di-O-caffeoylquinic acid (13), 1-O-caffeoyl-5-O-feruloylquinic acid (14), 4,5-di-O-caffeoylquinic acid (15), 4-O-feruloyl-5-O-caffeoylquinic acid (16), 4-O-caffeoyl-5-O-feruloylquinic acid (17), 4-O-feruloyl-5-O-caffeoylquinic methyl ester (18), 4,5-di-O-feruloylquinic acid (19), 3,4,5-tri-O-caffeoylquinic acid (20), respectively. The isolated caffeoylquinic acid compounds exhibited good inhibitory potential against different isoform proteins of phosphodiesterase family, with compound 9 showing an IC₅₀ value of 0.36 μmol/L for PDE4B inhibition. Conclusion Compound 1 is a new compound, named artemisinic acid A. Compounds 3—5, 8, 10—12, 14, 18 are identified from Artemisia genus for the first time. These compounds have a targeted inhibitory effect on phosphodiesterase.

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江苏省基础研究计划自然科学基金-前沿引领技术基础研究专项（SBK2023050003）;2021年国家中医药管理局岐黄学者支持项目（国中医药人教函〔2022〕6号）